Tuberculosis Research Center, Centers for Disease Control, Ministry of Health and Welfare, Taipei, Taiwan.
Reference Laboratory of Mycobacteriology, Centers for Disease Control, Ministry of Health and Welfare, Taipei, Taiwan.
Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0157320. doi: 10.1128/AAC.01573-20.
Discordant results between genotypic drug susceptibility testing (gDST) and phenotypic DST (pDST) for Mycobacterium tuberculosis isolates with disputed (discordance between gDST and pDST results) mutations affect rifampin (RIF)-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) treatments due to a lack of practical clinical guidelines. To investigate the role of disputed mutations in M. tuberculosis and TB treatment outcomes, initial isolates of 837 clinical RR- or MDR-TB cases confirmed during 2014 to 2018 were retested using agar-based RIF pDST and gene sequencing. MICs were determined for isolates with disputed mutations. Disputed mutations were identified in 77 (9.2%) M. tuberculosis isolates, including 50 (64.9%) and 14 (18.2%) phenotypically RIF- and rifabutin (RFB)-resistant isolates, respectively. The predominant single mutations were those encoding L533P (a change of L to P at position 533) (44.2%) and L511P (20.8%). Most of the isolates harboring mutations encoding L511P (87.5%), H526N (100%), D516Y (70.0%), and L533P (63.6%) had MICs of ≤1 mg/liter, whereas isolates harboring the mutation encoding H526L (75%) had a MIC of >1 mg/liter. Of the 63 cases with treatment outcomes available, 11 (17.5%) cases died, 1 (1.6%) case transferred out, and 51 (81%) cases had favorable outcomes, including 8 and 20 cases treated with standard-dose RIF- and RFB-containing regimens, respectively. Excluding cases that transferred out or received no or 1-day treatment, we observed statistically significant differences between the outcomes using active and inactive fluoroquinolones (FQs) ( = 0.008, odds ratio = 0.05 [95% confidence interval, 0.01 to 0.38]) in 57 cases (where active means a case susceptible to the drug and inactive means a case resistant to the drug or drug not used). We concluded that disputed mutations are not rare. Depending on the resources available, sequencing and/or MIC testing is recommended for better management of RR- and MDR-TB cases.
结核分枝杆菌分离株基因型药物敏感性试验（gDST）与表型药物敏感性试验（pDST）结果不一致（gDST 与 pDST 结果不一致）的突变会影响利福平（RIF）耐药（RR）和耐多药（MDR）结核病（TB）的治疗，因为缺乏实用的临床指南。为了研究有争议的突变在结核分枝杆菌和 TB 治疗结果中的作用，对 2014 年至 2018 年期间确认的 837 例临床 RR 或 MDR-TB 病例的初始分离株进行了重新检测，使用基于琼脂的 RIF pDST 和 基因测序。对有争议的突变的分离株进行了 MIC 测定。在 77 株结核分枝杆菌分离株（9.2%）中发现了有争议的突变，分别有 50 株（64.9%）和 14 株（18.2%）表型上对 RIF 和 rifabutin（RFB）耐药的分离株。主要的单一突变是编码 L533P（位置 533 处由 L 突变为 P）的突变（44.2%）和编码 L511P 的突变（20.8%）。携带 L511P 突变的大多数分离株（87.5%）、H526N（100%）、D516Y（70.0%）和 L533P（63.6%）的 MIC 值≤1mg/L，而携带 H526L 突变的分离株（75%）的 MIC 值>1mg/L。在 63 例可获得治疗结果的病例中，11 例（17.5%）死亡，1 例（1.6%）转出，51 例（81%）有良好的结果，包括 8 例和 20 例分别接受标准剂量 RIF 和 RFB 含药方案治疗。在 57 例病例中（排除转出或未接受或仅接受 1 天治疗的病例），排除了转出或未接受或仅接受 1 天治疗的病例，我们观察到使用活性和非活性氟喹诺酮类药物（FQs）之间的治疗结果存在统计学显著差异（ = 0.008，优势比=0.05 [95%置信区间，0.01 至 0.38]）。我们得出结论，有争议的突变并不罕见。根据现有资源，建议进行测序和/或 MIC 检测，以更好地管理 RR 和 MDR-TB 病例。
